The goal of this project is to develop zebrafish as a model system to investigate regeneration of oligodendrocytes, the myelinating cell type of the vertebrate central nervous system, from resident populations of neural stem and progenitor cells. The ability to promote formation of new oligodendrocytes might aid therapies to restore nervous system function following disease or injury. Zebrafish offer numerous advantages for studying neural regeneration. Zebrafish develop entirely outside the mother and embryos and young fish are optically clear, providing the opportunity for direct and extended observations of neural cells. To facilitate direct observation of oligodendrocytes, we have produced transgenic reporter gene lines that express fluorescent proteins in oligodendrocytes at all stages of their differentiation. Because they readily take up chemical compounds, our transgenic zebrafish can be used to screen for drugs that promote oligodendrocyte replacement. Thus, this work seeks to utilize the Zebrafish Chemical Screening Center to search for drugs that promote formation of oligodendrocytes. Neural diseases and injuries have devastating impacts on human health. This work will provide a foundation for identifying and investigating genes and drugs that promote neural regeneration and recovery.

R03MH076346

2005-09-15

2006-09-14